DESCRIPTION, OVERALL (provided by applicant): The Hopkins Digestive Diseases Basic Research Development Core Center is an NIDDK Research Development Center (DDBRDCC) which has been designed to advance basic science and translational digestive diseases research at the Johns Hopkins University School of Medicine and to foster collaborations and new directions of digestive (gastrointestinal and liver) diseases research by providing access for its members and associate members to Cores: A. Epithelial Proteomics Core;B. Imaging Core;C. Mouse Physiology Core. The DDBRDCC is a partnership between the JHUSOM and the members of this Center, with investment in personnel and equipment by the JHUSOM supplementing the Center budget. Core A, Epithelial Proteomics Core will help identify proteins that are differentially expressed in Gl tract/liver/kidney normally or in diseases of these organs, track interactions among proteins including identification of binding partners, examine protein turnover, map cleavage sites and determine post-translational modifications. The approaches will use 2D and liquid chromatography separations and mass spectrometry. This Core will provide a technician to interface with Core investigators for planning, quality control, and bioinformatics consultation. Core B, Imaging Core will make multiple types of cutting edge imaging and EM of epithelial cells available to DDBRDCC investigators and provide a Core Manager to help perform the studies. These include confocal and two-photon microscopy;use of a fluorometer, digital camera;and access to laser capture microscopy. Core B will also assist DDBRDCC investigators prepare intestine, liver, pancreas and kidney for EM. Core C, Mouse Physiology Core will provide advice in establishing mouse colonies, genotype mouse models of digestive diseases, make available metabolic cages and perform urine, stool, blood collections and analysis. This Core will also perform aortic perfusion of mice as part of intestinal, liver, pancreas, kidney procurement and preparation for Northern and Western analysis. This approach will also be used by Core C to remove, orient, fix, process, embed, section and mount these tissues to be used for light microscopy. Core C will make equipment available and instruction in its use for Ussing chamber/voltage clamp/active intestinal Na+ and Cl- transport studies. Administrative Operations will provide the communication, financial management and administrative functions of the DDBRDCC and organize the enrichment program (financed by non-Core sources).